Drug delivery device

ABSTRACT

The disclosure relates to a drug delivery device, comprising: an outer needle sleeve; a cartridge containing a dosage of a medicament and sealed with a sealing element that is arranged across an open distal end of the cartridge; a cartridge carrier adapted to hold the cartridge; a needle hub adapted to hold a double ended hollow needle; an inner needle sleeve arranged between the needle hub and the cartridge carrier; a removable cap coupled to the inner needle sleeve and adapted to cover and seal the needle; and a first locking mechanism adapted to lock the inner needle sleeve against axial movement in the proximal direction with respect to the cartridge carrier in an initial state, wherein in the initial state, the needle is spaced from the cartridge in the distal direction, and wherein the first locking mechanism is releasable by a rotational movement of the cap with respect to the outer needle sleeve.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of application Ser. No.15/736,627, filed on Dec. 14, 2017, which is the U. S. national stageentry under 35 USC § 371 of International Patent Application No.PCT/EP2016/063697, filed on Jun. 15, 2016, which claims priority toEuropean Patent Application No. 15172769.0, filed on Jun. 18, 2015, theentire contends of which are incorporated herein by reference.

TECHNICAL FIELD

The disclosure relates to a drug delivery device.

BACKGROUND

Administering an injection is a process which presents a number of risksand challenges for users and healthcare professionals, both mental andphysical. Pre-filled syringes with a syringe cartridge containing aselected dosage of a medicament for administering the medicament to apatient are known in the art. The cartridges may be stored in ablistered package so that they remain sterile until the time of use. Thecartridges include a hollow injection needle that is in fluidcommunication with the medicament stored in the cartridge. Thus, theinjection needle can be clogged after a long-term storage.

SUMMARY

An improved drug delivery device is disclosed herein that is configuredfor reducing the risk of a clogged needle during storage.

Implementations can include one or more of the following features.

According to the disclosure, a drug delivery device comprises: an outerneedle sleeve; a cartridge containing a medicament and sealed with asealing element that is arranged across an open distal end of thecartridge; a cartridge carrier adapted to hold the cartridge; a needlehub adapted to hold a double ended hollow needle; an inner needle sleevearranged between the needle hub and the cartridge carrier; a removablecap coupled to the inner needle sleeve and adapted to cover and seal theneedle; and a first locking mechanism adapted to lock the inner needlesleeve against axial movement in the proximal direction with respect tothe cartridge carrier in an initial state, wherein in the initial statethe double-ended hollow needle is spaced from the cartridge in thedistal direction; and wherein the first locking mechanism is releasableby a rotational movement of the cap with respect to the outer needlesleeve.

In the drug delivery device according to the disclosure, thedouble-ended hollow needle gets in contact with the medicament containedin the cartridge immediately before the start of a drug deliveryprocess. Thus, the drug delivery device reduces the risk for cloggingthe needle by the medicament compared with the related art, whereby atime required for drug delivery will not be increased. The double-endedhollow needle can be preassembled to the drug delivery device and willremain sterile and clean until the beginning of drug delivery. Here, theinitial position of the drug delivery device is a position in which thedevice would be presented to a user prior to use, whereby thedouble-ended hollow needle is not in fluid communication with themedicament stored in the cartridge. The sealing element seals themedicament stored in the cartridge against environmental influences andensures that the medicament remains within the cartridge before startingdrug delivery.

In an exemplary embodiment, an angle of the rotational movement of thecap with respect to the outer needle sleeve is in a range of 30 degreesto 45 degrees.

In an alternative embodiment, an angle of the rotational movement of thecap with respect to the outer needle sleeve is in a range of 30 degreesto 90 degrees.

In a further alternative embodiment, an angle of the rotational movementof the cap with respect to the outer needle sleeve is in more than 90degrees.

In an exemplary embodiment, the first locking mechanism comprises anumber of recesses arranged in the outer circumference of a distalportion of the cartridge carrier and a number of sleeve ribs arranged onan inner circumference of the inner needle sleeve and projectingradially inwards. Likewise, the ribs could be arranged outwardlyprojecting on the outer circumference of the distal portion of thecartridge carrier and the recesses could be arranged on the innercircumference of the inner needle sleeve.

When the drug delivery device is in the initial position, a distal endof the cartridge carrier couples to the sleeve ribs, wherein therecesses are angularly misaligned from the sleeve ribs. The firstlocking mechanism may then be released when the sleeve ribs engage intothe recesses due to the rotational movement of the cap, wherein theneedle hub and the needle sleeve move in the proximal direction withrespect to the cartridge carrier.

When the needle hub and the inner needle sleeve move in the proximaldirection with respect to the cartridge carrier, a needle tip of aproximal needle section pierces the sealing element. As a result, theneedle gets in fluid communication with the medicament stored in thecartridge.

In an exemplary embodiment, the coupling of the cap and the inner needlesleeve is achieved by a plurality of sleeve pins arranged on a distalend of the inner needle sleeve and projecting axially in a distaldirection and by a plurality of cap arms arranged on a distal end of thecap and projecting axially in a proximal direction. The needle hub maythen comprise a plurality of openings through which the sleeve pinsprojects. The number of openings may correspond with a number of sleevepins.

In an exemplary embodiment, the drug delivery device comprises a secondlocking mechanism adapted to lock the cap against axial removal from theouter needle sleeve. The second locking mechanism may be releasable whenthe first locking mechanism is released. Thus, an unintended removal ofthe cap is prevented before the needle has pierced the sealing element.

For example, the second locking mechanism includes a bayonet connectionbetween the cap and the outer needle sleeve allowing for a quick andeasy assembly and removal as well. The outer needle sleeve may compriseat least one bayonet slot including ramp sections that guide the caparms during rotational movement of the cap with respect to the outerneedle sleeve.

In an exemplary embodiment, the second locking mechanism comprises anaudible and/or tactile feedback for indicating the release of the firstlocking mechanism to a user. For example, the bayonet slot comprises aprotrusion, wherein the audible and/or tactile feedback will begenerated when a cap drive member passes the protrusion and hits theramp behind the protrusion.

In an exemplary embodiment, a spring is adapted to move the needle huband the inner sleeve in the proximal direction with respect to thecartridge carrier when the first locking mechanism is released. Thespring is coupled to the needle hub and the outer body, wherein aproximal end of the spring is coupled to the needle hub and a distal endof the spring is coupled to the outer needle sleeve.

In the initial state, the spring may bias the needle hub in the proximaldirection. Thus, a release of the first locking mechanism causes arelease of the spring. As a result, the needle hub and the inner sleeveare moved in the proximal direction with respect to the cartridgecarrier. The spring may be configured as a compressible spring.

Further scope of applicability of the present disclosure will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating exemplary embodiments of the disclosure, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the disclosure will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure will become more fully understood from thedetailed description given herein below and the accompanying drawings,which are given by way of illustration only, and thus, are notlimitative of the present disclosure, and wherein:

FIG. 1 is a schematic longitudinal detail section of an example of adrug delivery device in an initial state;

FIG. 2 is a schematic perspective view of an inner needle sleeve of thedrug delivery device;

FIG. 3 is a schematic perspective view of the inner needle sleeve of thedrug delivery device;

FIG. 4 is a schematic perspective view of a needle hub holding adouble-ended hollow needle;

FIG. 5 is a schematic cross section of the drug delivery device in theinitial state;

FIG. 6 is a schematic cross section of the drug delivery device with areleased first locking mechanism;

FIG. 7 is a schematic longitudinal detail section of the drug deliverydevice with the released first locking mechanism; and

FIG. 8 is a schematic cross section of the drug delivery device.

Corresponding parts are marked with the same reference symbols in allfigures.

DETAILED DESCRIPTION

FIG. 1 shows a schematic longitudinal detail section of a drug deliverydevice 1 according to an exemplary embodiment of the present disclosure.

The drug delivery device 1 is in an initial state S1. In the context ofthe present application, the initial position P1 of the drug deliverydevice 1 is a position in which the drug delivery device 1 would bepresented to the user prior to use before starting a drug deliveryprocess.

The drug delivery device 1 comprises a cartridge 2 forming a cavity thatcontains a dosage of a medicament. The cartridge 2 comprises an opendistal end which is sealed by a sealing element 2.1, e.g. a fluidimpermeable membrane. Furthermore, a stopper (not shown) may be disposedwithin the cartridge 2 limiting the cavity of the cartridge 2 in aproximal direction P and adapted for displacing the medicament from thecartridge 2 during drug delivery.

The cartridge 2 is mounted in a substantially cylindrically shaped andhollow cartridge carrier 3, thereby radially fixed due to a cylindricalshape of bars (not shown) and axially fixed by an undercut that receivesa cartridge crimp (not shown). The cartridge carrier 3 comprises acarrier rib 3.1 that is arranged proximally on an inner surface andprotrudes in a radial inward direction in a manner to engage a shoulderportion 2.2 of the cartridge 2. The cartridge carrier 3 furthercomprises a number of recesses 3.2 arranged on an outer circumference ofa distal portion. For example, the cartridge carrier 3 comprises tworecesses 3.2 extending in parallel to a longitudinal axis A of the drugdelivery device 1.

The recesses 3.2 are adapted to engage corresponding sleeve ribs 4.1 ofan inner needle sleeve 4. The inner needle sleeve 4 is substantiallycup-shaped and encloses at least the distal portion of the cartridgecarrier 3. In the initial state S1 of the drug delivery device 1, adistal end of the cartridge carrier 3 bears against the sleeve ribs 4.1,wherein the recesses 3.2 are angularly misaligned from the sleeve ribs4.1 and do thus not engage the sleeve ribs 4.1. The exemplary embodimentshown in FIGS. 1 and 2 illustrates one sleeve rib 4.1 respectively.

Likewise, the inner needle sleeve 4 may comprise two or more sleeve ribs4.1, wherein the number of recesses 3.2 is at least equal to the numberof sleeve ribs 4.1.

FIG. 2 shows the inner needle sleeve 4 in a schematic perspective. FIG.3 shows the inner needle sleeve 4 in a further perspective view.

The illustrated sleeve rib 4.1 is arranged on an inner surface of theinner needle sleeve 4 and projects radially inwards. The sleeve rib 4.1extends from a bottom end of the inner needle sleeve 4 in the proximaldirection P by a certain length, but not up to the proximal end of theinner needle sleeve 4. The length of the sleeve rib 4.1 may correspondwith the length of the recess 3.2. The bottom end of the inner needlesleeve 4 is a closed distal end comprising a central aperture 4.2through which a double ended hollow needle 5 may pass. The inner needlesleeve 4 further comprises a number of sleeve pins 4.3 adapted to engagewith a number of cap arms 6.1 of a cap 6 which will be described in moredetail below. The sleeve pins 4.3 protrude axially from the distal endin the distal direction D as illustrated in FIG. 3 . The inner needlesleeve 4 may comprise two sleeve pins 4.3 as illustrated in FIG. 3 .

Referring again to FIG. 1 , in the initial state S1, the inner needlesleeve 4 is locked against axial movement with respect to the cartridgecarrier 3 by a first locking mechanism L1. The first locking mechanismcomprises the sleeve ribs 4.1 and the recesses 3.2. As long as thesleeve ribs 4.1 are not engaged with the recesses 3.2, the cartridgecarrier 3 bears against the sleeve ribs 4.1 and the inner needle sleeve4 is thus not allowed to move in the proximal direction P with respectto the cartridge carrier 3.

The inner needle sleeve 4 is slidably arranged within an outer needlesleeve 7, whereby the inner needle sleeve 4 is locked against axialmovement with respect to the outer needle sleeve 7 by the first lockingmechanism L1. To guide a movement of the inner needle sleeve 4 withrespect to the outer needle sleeve 7 when the first locking mechanism L1is released, the outer needle sleeve 7 may comprise a section with areduced inner diameter in which a part of the inner needle sleeve 4 isslidably arranged. Likewise, the inner needle sleeve 4 may comprise aprojection on the outer circumference that is guided within a slotarranged on the inner circumference of the outer needle sleeve 7 or viceversa.

The inner needle sleeve 4 is coupled to a needle hub 8 that is shown inFIG. 4 in more detail, wherein FIG. 4 is a schematic perspective view ofthe needle hub 8.

The needle hub 8 comprises the needle 5 that is arranged through anaperture of a central stem. The needle 5 is thus divided into a proximalneedle section 5.1 and a distal needle section 5.2 by the central stem.

The distal needle section 5.2 comprises a needle tip that is targetedoutside the needle hub 8 in the distal direction D. The needle hub 8 issubstantially cup-shaped and adapted to enclose a distal portion of theinner needle sleeve 4, wherein the distal end of the inner needle sleeve4 bears against a bottom end of the needle hub 8. The aperture of theneedle hub 8 and the central aperture 4.2 of the inner needle sleeve 4are aligned to each other. Thus, the proximal needle section 5.1 passesthrough the central aperture 4.2 and comprises a needle tip that istargeted inside the inner needle sleeve 4 in the proximal direction P.In the initial state S1, the needle tip of the proximal needle section5.1 is distally spaced from the cartridge 2 and the cartridge carrier 3and is thus not in fluid communication with the medicament.

The bottom end of the needle hub 8 comprises two openings 8.1 configuredas curved elongated holes. The openings 8.1 are adapted to receive thesleeve pins 4.3 which are guidable within the openings 8.1 by the caparms 6.1, as described below.

The needle hub 8 further comprises a circular slot 8.2 in which aproximal end of a compressible spring 9 is arranged. The spring 9 isadapted to drive the needle hub 8 and the inner needle sleeve 4 in theproximal direction P with respect to the cartridge carrier 3 when thefirst locking mechanism L1 is released as illustrated in FIGS. 6 and 7 .Thereby, the spring 9 biases the needle hub 8 in the proximal directionP. The spring 9 is further coupled to the outer needle sleeve 7 with adistal end and thus additionally adapted to move the outer needle sleeve7 in the distal direction D with respect to the needle hub 8 to coverthe needle tip of the distal needle section 5.2 after the drug deliverydevice 1 is removed from an injection site.

Referring to the exemplary embodiment of the needle hub 8 shown in FIG.4 , the needle hub 8 further comprises two guiding slots 8.3 adapted toguide an axial movement of the needle hub 8 within the outer needlesleeve 7. The outer needle sleeve 7 comprises corresponding guidingprotrusions 7.2 engaging the guiding slots 8.3 as illustrated in FIG. 5.

The distal needle tip 5.2 is sealed and secured against environmentalinfluences by the cap 6 that is coupled to the outer needle sleeve 7 andto an outer body 10 which partially encloses the outer needle sleeve 7.In the initial state S1, the outer needle sleeve 7 projects beyond theouter body 10 in the distal direction D. The projecting section of theouter needle sleeve 7 is enclosed by the cap 6.

The cap 6 is locked to the outer needle sleeve 7 by a second lockingmechanism L2 which is adapted to prevent an unintended removal of thecap 6 before the first locking mechanism L1 is released. The secondlocking mechanism L2 may be configured as a bayonet connection. To thisend, the outer needle sleeve 7 may comprise at least one bayonet slot7.1 that is at least section-wise configured as a ramp for guiding a capdrive member 6.2 of the bayonet connection as illustrated in FIG. 8 inorder to provide a tactile feedback to the user when the cap 6 iscompletely turned and the first locking mechanism L1 is released.

The cap 6 comprises the cap arms 6.1 as mentioned above. For example,the cap 6 comprises two cap arms 6.1. The cap arms 6.1 are arranged onan outer circumference of a central stem configured as a hollow stem forreceiving the distal needle section 5.2. The stem projects into the cap6 in the proximal direction P. The cap arms 6.1 project radiallyoutwards from the outer circumference of the stem. For example, the caparms 6.1 extend along a longitudinal extension of the stem in parallelto the longitudinal axis A. The cap arms 6.1 are adapted to engage thesleeve pins 4.3 by angularly abutting the sleeve pins 4.3. In theinitial state S1, the sleeve pins 4.3 are arranged on one end of theopenings 8.1 respectively as illustrated in FIG. 5 .

FIG. 5 shows a cross section of the drug delivery device 1 in theinitial state S1.

In order to perform a drug delivery process, the drug delivery device 1may be activated as described in the following FIGS. 6 to 8 .

FIG. 6 shows a cross section of the drug delivery device 1 in anactivating state S2.

The cap 6 has been rotated around the longitudinal axis A with respectto the outer sleeve 7 and the outer body 10. Compared to FIG. 5 , thecap 6 has been rotated around the longitudinal axis A at an angle of 90degrees. In a not shown alternative embodiment, the cap 6 may be rotatedat an angle of more or less than 90 degrees.

Due to the engagement of the cap arms 6.1 and the sleeve pins 4.3, theinner needle sleeve 4 rotates with respect to the needle hub 8 and thecartridge carrier 3, following the rotational movement of the needle cap6 until the sleeve pins 4.3 abut against the other ends of the openings8.1 respectively. As the inner needle sleeve 4 rotates with respect tothe cartridge carrier 3, the recesses 3.2 engage the sleeve ribs 4.1.

The first locking mechanism L1 is now released allowing the inner needlesleeve 4 to move axially with respect to the cartridge carrier 3.Consequently, the compressed spring 9 relaxes and pushes the needle hub8 and the inner needle sleeve 4 in the proximal direction P with respectto the cartridge carrier 3 until the bottom end of the inner needlesleeve 4 abuts against the distal end of the cartridge carrier 3. Duringthe axial movement of the needle hub 8 and the inner needle sleeve 4,the needle tip of the proximal needle section 5.1 passes through theopen distal end of the cartridge carrier 3 and pierces the sealingelement 2.1. Thus, the needle 5 gets in fluid communication with themedicament stored in the cartridge 2.

FIG. 7 shows a longitudinal section of the drug delivery device 1 in theactivating state S2 with a released locking mechanism L1.

Due to the bayonet connection between the cap 6 and the outer needlesleeve 7, the second locking mechanism L2 can be released after thefirst locking mechanism L1 is released. The cap 6 is then allowed to beremoved by pulling the cap 6 off the outer needle sleeve 7.

FIG. 8 shows a schematic cross section of the drug delivery device 1.

The bayonet slot 7.1, in particular the section configured as a ramp maycomprise a protrusion (not shown) adapted to provide a tactile feedbackindicating to a user that the first locking mechanism L1 is released.The audible feedback will be generated when the cap drive member 6.2passes the protrusion and hits the bayonet slot 7.1 behind theprotrusion. The cap arms 6.2 are designed in such a manner that arelease force is adjustable due to a height difference of the rampsection of the bayonet slot 7.1 and the mechanical flexibility of thecap arms 6.2.

A drug delivery device 1 as it is described above may be suitable foruse as a pen-type device with an automatic needle insertion and/or anautomatic medicament delivery.

The terms “drug” or “medicament” are used herein to describe one or morepharmaceutically active compounds. As described below, a drug ormedicament can include at least one small or large molecule, orcombinations thereof, in various types of formulations, for thetreatment of one or more diseases. Exemplary pharmaceutically activecompounds may include small molecules; polypeptides, peptides andproteins (e.g., hormones, growth factors, antibodies, antibodyfragments, and enzymes); carbohydrates and polysaccharides; and nucleicacids, double or single stranded DNA (including naked and cDNA), RNA,antisense nucleic acids such as antisense DNA and RNA, small interferingRNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids maybe incorporated into molecular delivery systems such as vectors,plasmids, or liposomes. Mixtures of one or more of these drugs are alsocontemplated.

The term “drug delivery device” shall encompass any type of device orsystem configured to dispense a drug into a human or animal body.Without limitation, a drug delivery device may be an injection device(e.g., syringe, pen injector, auto injector, large-volume device, pump,perfusion system, or other device configured for intraocular,subcutaneous, intramuscular, or intravascular delivery), skin patch(e.g., osmotic, chemical, micro-needle), inhaler (e.g., nasal orpulmonary), implantable (e.g., coated stent, capsule), or feedingsystems for the gastro-intestinal tract. The presently described drugsmay be particularly useful with injection devices that include a needle,e.g., a small gauge needle.

The drug or medicament may be contained in a primary package or “drugcontainer” adapted for use with a drug delivery device. The drugcontainer may be, e.g., a cartridge, syringe, reservoir, or other vesselconfigured to provide a suitable chamber for storage (e.g., short- orlong-term storage) of one or more pharmaceutically active compounds. Forexample, in some instances, the chamber may be designed to store a drugfor at least one day (e.g., 1 to at least 30 days). In some instances,the chamber may be designed to store a drug for about 1 month to about 2years. Storage may occur at room temperature (e.g., about 20° C.), orrefrigerated temperatures (e.g., from about −4° C. to about 4° C.). Insome instances, the drug container may be or may include a dual-chambercartridge configured to store two or more components of a drugformulation (e.g., a drug and a diluent, or two different types ofdrugs) separately, one in each chamber. In such instances, the twochambers of the dual-chamber cartridge may be configured to allow mixingbetween the two or more components of the drug or medicament prior toand/or during dispensing into the human or animal body. For example, thetwo chambers may be configured such that they are in fluid communicationwith each other (e.g., by way of a conduit between the two chambers) andallow mixing of the two components when desired by a user prior todispensing. Alternatively or in addition, the two chambers may beconfigured to allow mixing as the components are being dispensed intothe human or animal body.

The drug delivery devices and drugs described herein can be used for thetreatment and/or prophylaxis of many different types of disorders.Exemplary disorders include, e.g., diabetes mellitus or complicationsassociated with diabetes mellitus such as diabetic retinopathy,thromboembolism disorders such as deep vein or pulmonarythromboembolism. Further exemplary disorders are acute coronary syndrome(ACS), angina, myocardial infarction, cancer, macular degeneration,inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis.

Exemplary drugs for the treatment and/or prophylaxis of diabetesmellitus or complications associated with diabetes mellitus include aninsulin, e.g., human insulin, or a human insulin analogue or derivative,a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptoragonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4(DPP4) inhibitor, or a pharmaceutically acceptable salt or solvatethereof, or any mixture thereof. As used herein, the term “derivative”refers to any substance which is sufficiently structurally similar tothe original substance so as to have substantially similar functionalityor activity (e.g., therapeutic effectiveness).

Exemplary insulin analogues are Gly(A21), Arg(B31), Arg(B32) humaninsulin (insulin glargine); Lys(B3), Glu(B29) human insulin; Lys(B28),Pro(B29) human insulin; Asp(B28) human insulin; human insulin, whereinproline in position B28 is replaced by Asp, Lys, Leu, Val or Ala andwherein in position B29 Lys may be replaced by Pro; Ala(B26) humaninsulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30)human insulin.

Exemplary insulin derivatives are, for example, B29-N-myristoyl-des(B30)human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoylhuman insulin; B29-N-palmitoyl human insulin; B28-N-myristoylLysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) humaninsulin; B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin. Exemplary GLP-1, GLP-1analogues and GLP-1 receptor agonists are, for example:Lixisenatide/AVE0010/ZP10/Lyxumia,Exenatide/Exendin-4/Byetta/Bydureon/ITCA 650/AC-2993 (a 39 amino acidpeptide which is produced by the salivary glands of the Gila monster),Liraglutide/Victoza, Semaglutide, Taspoglutide, Syncria/Albiglutide,Dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054,Langlenatide/HM-11260C, CM-3, GLP-1 Eligen, ORMD-0901, NN-9924, NN-9926,NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697,DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034. MOD-6030,CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN andGlucagon-Xten.

An exemplary oligonucleotide is, for example: mipomersen/Kynamro, acholesterol-reducing antisense therapeutic for the treatment of familialhypercholesterolemia.

Exemplary DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin,Saxagliptin, Berberine.

Exemplary hormones include hypophysis hormones or hypothalamus hormonesor regulatory active peptides and their antagonists, such asGonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin),Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin,Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

Exemplary polysaccharides include a glucosaminoglycane, a hyaluronicacid, a heparin, a low molecular weight heparin or an ultra-lowmolecular weight heparin or a derivative thereof, or a sulphatedpolysaccharide, e.g. a poly-sulphated form of the above-mentionedpolysaccharides, and/or a pharmaceutically acceptable salt thereof. Anexample of a pharmaceutically acceptable salt of a poly-sulphated lowmolecular weight heparin is enoxaparin sodium. An example of ahyaluronic acid derivative is Hylan G-F 20/Synvisc, a sodiumhyaluronate.

The term “antibody”, as used herein, refers to an immunoglobulinmolecule or an antigen-binding portion thereof. Examples ofantigen-binding portions of immunoglobulin molecules include F(ab) andF(ab′)₂ fragments, which retain the ability to bind antigen. Theantibody can be polyclonal, monoclonal, recombinant, chimeric,de-immunized or humanized, fully human, non-human, (e.g., murine), orsingle chain antibody. In some embodiments, the antibody has effectorfunction and can fix complement. In some embodiments, the antibody hasreduced or no ability to bind an Fc receptor. For example, the antibodycan be an isotype or subtype, an antibody fragment or mutant, which doesnot support binding to an Fc receptor, e.g., it has a mutagenized ordeleted Fc receptor binding region.

The terms “fragment” or “antibody fragment” refer to a polypeptidederived from an antibody polypeptide molecule (e.g., an antibody heavyand/or light chain polypeptide) that does not comprise a full-lengthantibody polypeptide, but that still comprises at least a portion of afull-length antibody polypeptide that is capable of binding to anantigen. Antibody fragments can comprise a cleaved portion of a fulllength antibody polypeptide, although the term is not limited to suchcleaved fragments. Antibody fragments that are useful in the presentdisclosure include, for example, Fab fragments, F(ab′)2 fragments, scFv(single-chain Fv) fragments, linear antibodies, monospecific ormultispecific antibody fragments such as bispecific, trispecific, andmultispecific antibodies (e.g., diabodies, triabodies, tetrabodies),minibodies, chelating recombinant antibodies, tribodies or bibodies,intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP),binding-domain immunoglobulin fusion proteins, camelized antibodies, andVHH containing antibodies. Additional examples of antigen-bindingantibody fragments are known in the art.

The terms “Complementarity-determining region” or “CDR” refer to shortpolypeptide sequences within the variable region of both heavy and lightchain polypeptides that are primarily responsible for mediating specificantigen recognition. The term “framework region” refers to amino acidsequences within the variable region of both heavy and light chainpolypeptides that are not CDR sequences, and are primarily responsiblefor maintaining correct positioning of the CDR sequences to permitantigen binding. Although the framework regions themselves typically donot directly participate in antigen binding, as is known in the art,certain residues within the framework regions of certain antibodies candirectly participate in antigen binding or can affect the ability of oneor more amino acids in CDRs to interact with antigen.

Exemplary antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).

The compounds described herein may be used in pharmaceuticalformulations comprising (a) the compound(s) or pharmaceuticallyacceptable salts thereof, and (b) a pharmaceutically acceptable carrier.The compounds may also be used in pharmaceutical formulations thatinclude one or more other active pharmaceutical ingredients or inpharmaceutical formulations in which the present compound or apharmaceutically acceptable salt thereof is the only active ingredient.Accordingly, the pharmaceutical formulations of the present disclosureencompass any formulation made by admixing a compound described hereinand a pharmaceutically acceptable carrier.

Pharmaceutically acceptable salts of any drug described herein are alsocontemplated for use in drug delivery devices. Pharmaceuticallyacceptable salts are for example acid addition salts and basic salts.Acid addition salts are e.g. HCl or HBr salts. Basic salts are e.g.salts having a cation selected from an alkali or alkaline earth metal,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are known to those of skill in thearts.

Pharmaceutically acceptable solvates are for example hydrates oralkanolates such as methanolates or ethanolates.

Those of skill in the art will understand that modifications (additionsand/or removals) of various components of the substances, formulations,apparatuses, methods, systems and embodiments described herein may bemade without departing from the full scope and spirit of the presentdisclosure, which encompass such modifications and any and allequivalents thereof.

LIST OF REFERENCES

-   -   1 drug delivery device    -   2 cartridge    -   2.1 sealing element    -   2.2 shoulder portion    -   3 cartridge carrier    -   3.1 carrier rib    -   3.2 recess    -   4 inner needle sleeve    -   4.1 sleeve rib    -   4.2 central aperture    -   4.3 sleeve pin    -   5 needle    -   5.1 proximal needle section    -   5.2 distal needle section    -   6 cap    -   6.1 cap arm    -   6.2 cap drive member    -   7 outer needle sleeve    -   7.1 bayonet slot    -   7.2 guiding protrusions    -   8 needle hub    -   8.1 opening    -   8.2 slot    -   8.3 guiding slot    -   9 spring    -   10 outer body    -   A longitudinal axis    -   D distal direction    -   P proximal direction    -   L1 first locking mechanism    -   L2 second locking mechanism    -   S1 initial state    -   S2 activating state

The invention claimed is:
 1. A drug delivery device comprising: an outerneedle sleeve; a cartridge carrier adapted to hold a cartridge; a needlehub adapted to hold a double ended hollow needle; an inner needle sleevearranged between the needle hub and the cartridge carrier; a removablecap coupled to the inner needle sleeve and adapted to cover and seal theneedle; and a cap locking mechanism adapted to lock the cap againstaxial removal from the outer needle sleeve; wherein the cartridgecarrier is arranged within the inner needle sleeve.
 2. The drug deliverydevice according to claim 1, wherein the cap locking mechanism includesa bayonet connection between the cap and the outer needle sleeve.
 3. Thedrug delivery device according to claim 2, wherein the outer needlesleeve comprises at least one bayonet slot having ramp sections thatguide arms of the cap during rotational movement of the cap with respectto the outer needle sleeve.
 4. The drug delivery device according toclaim 1, wherein the inner needle sleeve comprises a plurality of sleevepins on a distal end of the inner needle sleeve, the plurality of sleevepins projecting axially in a distal direction, and the cap comprises aplurality of cap arms projecting axially in a proximal direction andengaging the plurality of sleeve pins.
 5. The drug delivery deviceaccording to claim 4, wherein the needle hub comprises a plurality ofopenings through which the plurality of sleeve pins project.
 6. The drugdelivery device according to claim 1, comprising a sleeve lockingmechanism adapted to lock the inner needle sleeve against axial movementin a proximal direction with respect to the cartridge carrier in aninitial state.
 7. The drug delivery device according to claim 6, whereinthe sleeve locking mechanism is arranged between the inner needle sleeveand the cartridge carrier and is releasable by a rotational movement ofthe cap with respect to the outer needle sleeve.
 8. The drug deliverydevice according to claim 7, wherein an angle of the rotational movementof the cap with respect to the outer needle sleeve is in a range ofabout 30 degrees to about 45 degrees.
 9. The drug delivery deviceaccording to claim 7, wherein an angle of the rotational movement of thecap with respect to the outer needle sleeve is in a range of about 30degrees to about 90 degrees.
 10. The drug delivery device according toclaim 7, wherein an angle of the rotational movement of the cap withrespect to the outer needle sleeve is more than about 90 degrees. 11.The drug delivery device according to claim 6, wherein the sleevelocking mechanism comprises: a plurality of recesses arranged in anouter circumference of a distal portion of the cartridge carrier; and aplurality of sleeve ribs arranged on an inner circumference of the innerneedle sleeve and projecting radially inwards.
 12. The drug deliverydevice according to claim 11, wherein in the initial state, a distal endof the cartridge carrier is coupled to the sleeve ribs, wherein therecesses are angularly misaligned from the sleeve ribs.
 13. The drugdelivery device according to claim 11, wherein the sleeve lockingmechanism is released when the sleeve ribs engage into the recesses,such that the needle hub and the inner needle sleeve move in theproximal direction with respect to the cartridge carrier.
 14. The drugdelivery device according to claim 6, wherein the cap locking mechanismis releasable when the sleeve locking mechanism is released.
 15. Thedrug delivery device according to claim 6, wherein the cap lockingmechanism comprises one or both of an audible or tactile feedback forindicating that the sleeve locking mechanism has been released.
 16. Thedrug delivery device according to claim 6, comprising a spring adaptedto move the needle hub and the inner needle sleeve in the proximaldirection with respect to the cartridge carrier when the sleeve lockingmechanism is released.
 17. The drug delivery device according to claim16, wherein a proximal end of the spring is coupled to the needle huband a distal end of the spring is coupled to the outer needle sleeve,and wherein the spring biases the needle hub in the proximal directionin the initial state.
 18. The drug delivery device according to claim 1,comprising a cartridge containing a dose of a medicament, the cartridgesealed by a sealing element arranged across an open distal end of thecartridge, wherein in an initial state, the needle is spaced from thecartridge in a distal direction.
 19. A drug delivery device comprising:an outer needle sleeve; a cartridge carrier adapted to hold a cartridge;a needle hub adapted to hold a double ended hollow needle; an innerneedle sleeve arranged between the needle hub and the cartridge carrier;a removable cap coupled to the inner needle sleeve and adapted to coverand seal the needle; and a cap locking mechanism adapted to lock the capagainst axial removal from the outer needle sleeve, wherein the outerneedle sleeve is movable with respect to the cartridge carrier; whereinthe cartridge carrier is arranged within the inner needle sleeve.
 20. Adrug delivery device comprising: an outer needle sleeve; a cartridgecarrier adapted to hold a cartridge; a needle hub adapted to hold adouble ended hollow needle; an inner needle sleeve arranged between theneedle hub and the cartridge carrier, wherein the inner needle sleeve iswithin the needle hub; a removable cap coupled to the inner needlesleeve and adapted to cover and seal the needle; and a cap lockingmechanism adapted to lock the cap against axial removal from the outerneedle sleeve; wherein the cartridge carrier is arranged within theinner needle sleeve.